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-Structure paper
タイトル | A naturally arising broad and potent CD4-binding site antibody with low somatic mutation. |
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ジャーナル・号・ページ | Sci Adv, Vol. 8, Issue 32, Page eabp8155, Year 2022 |
掲載日 | 2022年8月12日 |
著者 | Christopher O Barnes / Till Schoofs / Priyanthi N P Gnanapragasam / Jovana Golijanin / Kathryn E Huey-Tubman / Henning Gruell / Philipp Schommers / Nina Suh-Toma / Yu Erica Lee / Julio C Cetrulo Lorenzi / Alicja Piechocka-Trocha / Johannes F Scheid / Anthony P West / Bruce D Walker / Michael S Seaman / Florian Klein / Michel C Nussenzweig / Pamela J Bjorkman / |
PubMed 要旨 | The induction of broadly neutralizing antibodies (bNAbs) is a potential strategy for a vaccine against HIV-1. However, most bNAbs exhibit features such as unusually high somatic hypermutation, ...The induction of broadly neutralizing antibodies (bNAbs) is a potential strategy for a vaccine against HIV-1. However, most bNAbs exhibit features such as unusually high somatic hypermutation, including insertions and deletions, which make their induction challenging. VRC01-class bNAbs not only exhibit extraordinary breadth and potency but also rank among the most highly somatically mutated bNAbs. Here, we describe a VRC01-class antibody isolated from a viremic controller, BG24, that is much less mutated than most relatives of its class while achieving comparable breadth and potency. A 3.8-Å x-ray crystal structure of a BG24-BG505 Env trimer complex revealed conserved contacts at the gp120 interface characteristic of the VRC01-class Abs, despite lacking common CDR3 sequence motifs. The existence of moderately mutated CD4-binding site (CD4bs) bNAbs such as BG24 provides a simpler blueprint for CD4bs antibody induction by a vaccine, raising the prospect that such an induction might be feasible with a germline-targeting approach. |
リンク | Sci Adv / PubMed:35960796 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 2.25 - 4 Å |
構造データ | EMDB-26443, PDB-7ucg: PDB-7uce: PDB-7ucf: |
化合物 | ChemComp-HOH: ChemComp-NAG: ChemComp-FUC: |
由来 |
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キーワード | VIRAL PROTEIN/IMMUNE SYSTEM / broadly neutralizing antibody / bNAb / HIV-1 / CD4 binding site / VH1-2 / VRC01-class / antiviral protein / VIRAL PROTEIN-IMMUNE SYSTEM complex |